? Current small molecule covalent inhibitors use Michael addition reaction of sulfhydryl (-SH) with Michael acceptors to target Cysteine(Cysteine)
? The terminal amino group (-NH2) of Lysine is another residue that can form covalent bonds, hydrogen bonds or other strong interactions with small molecules
? It is difficult for catalytical lysine to acquire adoptive mutation
? Small molecule inhibitors that target catalytic lysine are expected to solve the problem of TKI acquired resistance
? Design warhead targeting lysine based on the target protein’s structure
? Time-dependent in vivo and in vitro screening methods (lysine's covalent reaction or strong interaction leading to slow-off effects)
